The goal of this research program is to develop a flexible, compact, and passive fiber optic probe that is capable of axially scanning the tissue layers for cancer detection and diagnostic, and then demonstrate the value of the proposed sources for in vivo biomedical spectroscopy and endoscopy. The innovation of the proposed fiber optic probe is based on the new concept of simultaneous spatial and temporal focusing (SSTF) that was recently demonstrated in multiphoton imaging, where, in addition to conventional spatial focusing, an extra degree of axial confinement is achieved by temporally focusing an ultrashort pulse. We show that by adjusting the spectral phase of the input pulse at the proximal end of the fiber probe, we can scan the focal plane in an SSTF setup at the distal end remotely. Thus, a passive, ultracompact fiber probe can be achieved that provides high resolution z-sectioning of multiphoton excited fluorescence and/or harmonic generation over a scan depth of hundreds of microns. Leveraging the latest theoretical and experimental development of SSTF, and taking full advantage of the recent advancement of large mode area fiber for pulse delivery and signal collection, the proposed research program aims to create a practical and robust fiber optic probe that is tailored specifically for cancer detection and diagnostics. This research program involves close collaboration between the PI and Co-PI (Dr. Zipfel). The combined expertise of the research team includes all of the science and technologies required for conducting the proposed research. The proposed program, if successfully completed, leads to a novel fiber optic probe for early cancer detection and diagnosis. The advantage of multiphoton excitation through the flexible fiber probe, combined with the remote axial scanning capability, allows depth resolved signal excitation and detection, and can provide significantly improved diagnostic signature for non- invasive early cancer detection. Furthermore, the proposed fiber probe for multiphoton endoscopic spectroscopy is highly practical in a clinical environment, providing the possibility of rapid commercialization and having an immediate real-world impact. [unreadable] [unreadable] [unreadable]